Combinations of agents to treat hematological malignancies
AssigneeOregon Health & Science University
InventorsJeffrey Tyner, Stephen Kurtz, Brian Druker, Elie Traer, Christopher Eide, Motomi Mori, Andrew Kaempf
Life of this patent
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Abstract
Methods of treating acute myeloid leukemia, chronic lymphocytic leukemia and myeloproliferative neoplasms that involve the administration of combinations of small molecule compounds are disclosed.
Claims149
A method of identifying a subject with JQ1/palbociclib-responsive acute myeloid leukemia comprising:
- obtaining a biological sample from a living human patient with acute myeloid leukemia;
- detecting whether a DNMT3A mutation is present or absent in the biological sample by contacting the biological sample with a probe that binds to DNMT3A;
- and
- detecting binding between the probe and the DNMT3A,
- wherein the subject is identified as having JQ1/palbociclib-responsive acute myeloid leukemia if mutated DNMT3A is detected in the sample based on the binding of the probe.
A method of identifying a subject with JQ1/palbociclib-responsive acute myeloid leukemia and treating the subject comprising:
- obtaining a biological sample from a living human patient with acute myeloid leukemia;
- detecting whether mutated DNMT3A is present or absent in the biological sample;
- identifying the subject as having JQ1/palbociclib-responsive acute myeloid leukemia when mutated DNMT3A is detected in the biological sample;
- and
- administering an effective amount of JQ1 and palbociclib to the subject.
A method of providing a targeted combination therapy to a human patient in need thereof comprising:
- identifying a human patient with acute myeloid leukemia and a DNMT3A mutation;
- and
- administering a therapeutically effective amount of JQ1 and a CDK4/6 inhibitor to the human patient,
- thereby providing a targeted combination therapy to the human patient, wherein the CDK4/6 inhibitor is palbociclib.
A method of identifying a subject with JQ1/sorafenib-responsive acute myeloid leukemia comprising:
- obtaining a biological sample from a living human patient with acute myeloid leukemia;
- detecting whether NPM1 is mutated in the biological sample by contacting the biological sample with a probe that binds to NPM1;
- detecting binding between the probe and the mutated NPM1,
- wherein the subject is identified as having JQ1/sorafenib-responsive acute myeloid leukemia if mutated NPM1 is detected in the sample based on the binding between the probe and the NPM1.
A method of identifying a subject with JQ1/sorafenib-responsive acute myeloid leukemia and treating the subject comprising:
- obtaining a biological sample from a living human patient with acute myeloid leukemia;
- detecting whether mutated NPM1 is present or absent in the biological sample;
- identifying the subject as having JQ1/sorafenib-responsive acute myeloid leukemia when mutated NPM1 is detected in the biological sample;
- and
- administering an effective amount of JQ1 and sorafenib to the subject.
A method of providing a targeted combination therapy to a human patient in need thereof comprising:
- identifying a human patient with acute myeloid leukemia and a NPM1 mutation;
- and
- administering a therapeutically effective amount of JQ1 and a tyrosine kinase inhibitor to the human patient,
- thereby providing a targeted combination therapy to the human patient, wherein the tyrosine kinase inhibitor is sorafenib.
A method of identifying a subject with ruxolitinib/cabozanatinib-responsive acute myeloid leukemia comprising:
- obtaining a biological sample from a living human patient with acute myeloid leukemia;
- and
- detecting whether a normal karyotype is present or absent in the biological sample by contacting the sample with one or more dyes that stain chromosomes and visualizing the chromosomes to detect the karyotype of the sample;
- wherein the subject is identified as having ruxolitinib/cabozanatinib-responsive acute myeloid leukemia if a normal karyotype is detected in the sample.
A method of identifying a subject with ruxolitinib/cabozanatinib-responsive acute myeloid leukemia and treating the subject comprising:
- obtaining a biological sample from a living human patient with acute myeloid leukemia;
- detecting whether a normal karyotype is present or absent in the biological sample;
- identifying the subject as having ruxolitinib/cabozanatinib-responsive acute myeloid leukemia when a normal karyotype is detected in the biological sample;
- and
- administering an effective amount of ruxolitinib and cabozanatinib to the subject.
A method of providing a targeted combination therapy to a human patient in need thereof comprising:
- identifying a human patient with acute myeloid leukemia and a normal karyotype;
- and
- administering a therapeutically effective amount of cabozanatinib and a tyrosine kinase inhibitor to the human patient,
- thereby providing a targeted combination therapy to the human patient, wherein the tyrosine kinase inhibitor is ruxolitinib.
A method of identifying a subject with idelalisib/quizartinib-responsive acute myeloid leukemia comprising:
- obtaining a biological sample from a living human patient with acute myeloid leukemia;
- and
- detecting whether the biological sample is positive for complex karyotype by contacting the sample with one or more dyes that bind to chromosomes and analyzing the chromosomes by microscopy to identify chromosomal aberrations,
- wherein the subject is identified as having idelalisib/quizartinib-responsive acute myeloid leukemia if the sample is identified as positive for complex karyotype.
A method of identifying a subject with idelalisib/quizartinib-responsive acute myeloid leukemia and treating the subject comprising:
- obtaining a biological sample from a living human patient with acute myeloid leukemia;
- detecting whether a complex karyotype is present or absent in the biological sample;
- identifying the subject as having idelalisib/quizartinib-responsive acute myeloid leukemia when a complex karyotype is detected in the biological sample;
- and
- administering an effective amount of idelalisib and quizartinib to the subject.
A method of providing a targeted combination therapy to a human patient in need thereof comprising:
- identifying a human patient with acute myeloid leukemia and a complex karyotype;
- and
- administering a therapeutically effective amount of a PI3 kinase inhibitor and a FLT3/CSF1R inhibitor to the human patient,
- thereby providing a targeted combination therapy to the human patient, wherein the PI3 kinase inhibitor is idelalasib and the FLT3/CSF1R inhibitor is quizartinib.
A method of identifying a subject with venetoclax/JQ1-responsive acute myeloid leukemia comprising:
- obtaining a biological sample from a living human patient with acute myeloid leukemia;
- detecting the presence or absence of CD11b in the biological sample by contacting the sample with an anti-CD11b antibody or a CD11b probe and detecting binding between the antibody or probe and CD11b,
- wherein the subject is identified as having venetoclax/JQ1-responsive acute myeloid leukemia if CD11b is present in the sample.
A method of identifying a subject with venetoclax/JQ1-responsive acute myeloid leukemia and treating the subject comprising:
- obtaining a biological sample from a living human patient with acute myeloid leukemia;
- detecting whether CD11b is expressed in the biological sample;
- identifying the subject as having venetoclax/JQ1-responsive acute myeloid leukemia when CD11b is detected in the biological sample;
- and
- administering an effective amount of venetoclax and JQ1 to the subject.
A method of providing a targeted combination therapy to a human patient in need thereof comprising:
- identifying a human patient who has acute myeloid leukemia and is positive for CD11b expression;
- and
- administering a therapeutically effective amount of a Bcl2 inhibitor and JQ1 to the human patient,
- thereby providing a targeted combination therapy to the human patient, wherein the Bcl2 inhibitor is venetoclax.
A method of identifying a subject with venetoclax/doramapimod-responsive acute myeloid leukemia comprising:
- obtaining a biological sample from a human patient with acute myeloid leukemia;
- and
- detecting the presence or absence of CD58 in the biological sample by contacting the sample with an anti-CD58 antibody or a CD58 probe and detecting binding between the anti-CD58 antibody or a CD58 probe and CD58,
- wherein the patient is identified as having venetoclax/doramapimod-responsive acute myeloid leukemia if CD58 is present in the sample.
A method of identifying a subject with venetoclax/doramapimod-responsive acute myeloid leukemia and treating the subject comprising:
- obtaining a biological sample from a human patient with acute myeloid leukemia;
- detecting whether CD58 is expressed in the biological sample;
- identifying the patient as having venetoclax/doramapimod-responsive acute myeloid leukemia when CD58 is detected in the biological sample;
- and
- administering an effective amount of venetoclax and doramapimod to the subject.
A method of providing a targeted combination therapy to a human patient in need thereof comprising:
- identifying a human patient with acute myeloid leukemia and CD58 expression;
- and
- administering a therapeutically effective amount of a Bcl2 inhibitor and doramapimod to the human patient,
- thereby providing a targeted combination therapy to the human patient, wherein the Bcl2 inhibitor is venetoclax.
A method of identifying a subject with chronic lymphoblastic leukemia that is responsive to combined therapy with (i) palbociclib and (ii) venetoclax or trametinib comprising:
- obtaining a biological sample from a human patient with chronic lymphoblastic leukemia;
- detecting whether there is a chromosome 13q deletion in the biological sample by contacting the sample with (i) a labelled probe that bind to chromosome 13q or (ii) a dye that stains chromosomes for microscopy analysis;
- and
- detecting binding between the probes or the dye and chromosome 13q,
- wherein the subject is identified as having chronic lymphoblastic leukemia that is responsive to combined therapy with (i) palbociclib and (ii) venetoclax or trametinib if a chromosome 13q deletion is detected in the sample.
A method of (a) identifying a subject with chronic lymphoblastic leukemia that is responsive to combined therapy with (i) palbociclib and (ii) venetoclax or trametinib and (b) treating the subject comprising:
- obtaining a biological sample from a living human patient with chronic lymphoblastic leukemia;
- detecting whether a chromosome 13q deletion is present in the biological sample;
- identifying the subject as having chronic lymphoblastic leukemia that is responsive to combined therapy with (i) palbociclib and (ii) venetoclax or trametinib when a chromosome 13q deletion is detected in the biological sample;
- and
- administering an effective amount of (i) palbociclib and (ii) venetoclax or trametinib to the subject.
A method of providing a targeted combination therapy to a human patient in need thereof comprising:
- identifying a human patient with chronic lymphoblastic leukemia and a chromosome 13q deletion;
- and
- administering a therapeutically effective amount of (i) a CDK4/6 inhibitor and (ii) a Bcl2 inhibitor or a MEK inhibitor,
- thereby providing a targeted combination therapy to the human patient, wherein the CDK4/6 inhibitor is palbociclib, the Bcl2 inhibitor is venetoclax, and the MEK inhibitor trametinib.
Dependencies are inferred from the claim text.